Analysis of Whole Blood and Urine Trace Elements in Children with Autism Spectrum Disorders and Autistic Behaviors.

The relationship between trace elements and neurological development is an emerging research focus. We performed a case-control study to explore (1) the differences of 13 trace elements chromium (Cr), manganese (Mn), cobalt (Co), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), stannum (Sn), stibium (Sb), mercury (Hg), titanium (TI), and plumbum (Pb) concentration in whole blood and urine between autism spectrum disorder (ASD) children and their typical development peers, and (2) the association between the 13 trace elements and core behaviors of ASD. Thirty ASD subjects (cases) and 30 age-sex-matched healthy subjects from Baise City, Guangxi Zhuang Autonomous Region, China, were recruited. Element analysis was carried out by inductively coupled plasma-optical emission spectrometry. Autistic behaviors were assessed using Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Children Neuropsychological and Behavior Scale (CNBS). The whole blood concentrations of Mo (p = 0.004), Cd (0.007), Sn (p = 0.003), and Pb (p = 0.037) were significantly higher in the ASD cases than in the controls. Moreover, Se (0.393), Hg (0.408), and Mn (- 0.373) concentrations were significantly correlated between whole blood and urine levels in ASD case subjects. There were significant correlations between whole blood Sb (0.406), Tl (0.365), Mo (- 0.4237), Mn (- 0.389), Zn (0.476), and Se (0.375) levels and core behaviors of ASD. Although the mechanism of trace element imbalance in ASD is unclear, these data demonstrate that core behaviors of ASD may be affected by certain trace elements. Further studies are recommended for exploring the mechanism of element imbalance and providing corresponding clinical treatment measures.

Abnormal cortical-striatal-thalamic-cortical circuit centered on the thalamus in MDD patients with somatic symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: Somatic symptoms are common comorbidities of major depressive disorder (MDD), and negatively impact the course and severity of the disease. In order to enrich the understanding of the pathological mechanism and clarify the neurobiological basis of somatic symptoms in depression, we attempted to explore the changes of brain structure and function in a large sample between depression with and without somatic symptoms. METHODS: Structure magnetic resonance imaging (MRI) data were collected from 342 patients with somatic symptoms (SD), 208 patients without somatic symptoms (NSD), and 510 healthy controls (HCs) based on the REST-meta-MDD project. We analyzed the whole brain VBM maps of the three groups, and combined with weight degree centrality (DC) index, we investigated whether the brain regions with gray matter volume (GMV) and gray matter density (GMD) abnormalities in MDD patients with somatic symptoms had corresponding brain functional abnormalities. RESULTS: Between depression with and without somatic symptoms, we found that there are extensive GMV and GMD differences involving cortical regions such as the temporal lobe, occipital lobe, and insula, as well as subcortical brain regions such as thalamus and striatum. The comparison results of weight DC signals of GMV and GMD abnormal clusters between the SD and NSD groups were basically consistent with the GMV and GMD abnormal clusters. CONCLUSION: The results indicate that the structure and function of cortical-striatal-thalamic-cortical (CSTC) circuit centered on the thalamus were abnormal in MDD patients with somatic symptoms. This may be the neurobiological basis of somatic symptoms in MDD.

Injuries in Left Corticospinal Tracts, Forceps Major, and Left Superior Longitudinal Fasciculus (Temporal) as the Quality Indicators for Major Depressive Disorder.

At present, the etiology and pathogenesis of major depressive disorder (MDD) are still not clear. Studies have found that the risk of first-degree relatives of MDD is 2-3 times that of the general population. Diffusion tensor imaging (DTI) has been previously used to explore the pathogenesis of MDD. The purpose of this study is to explore the etiology of MDD by DTI and further to explore the correlation between its clinical characteristics and the structural changes of white matter in the brain. The study included 27 first-episode, drug-naive patients with MDD, 16 first-degree relatives without MDD, and 28 healthy control subjects with no family history of MDD (HC). Results showed that the fractional anisotropy (FA) differences among the three groups were mainly in the left anterior thalamic radiation (LATR), right anterior thalamic radiation (RATR), left corticospinal tracts (LCST), forceps major (FMa), right inferior longitudinal fasciculus (RILF), and left superior longitudinal fasciculus (temporal) (LSLF(T)). Among the 6 sites, LCST, FMa, and LSLF(T) showed significant differences between MDD and First-degree relatives compared to HC. MDD patients had significant emotional symptoms, somatic symptoms, and cognitive impairment. FMa FA was significantly positively correlated with delayed memory score (r = 0.43, P = 0.031), and RILF FA was significantly negatively correlated with the FSS score (r = -0.42, P = 0.028). These results revealed that the white matter characteristics of MDD-susceptible patients were LCST, FMa, and LSLF(T) lesions, all of which may be quality indicators of MDD.

Functional connectivity between the thalamus and the primary somatosensory cortex in major depressive disorder: a resting-state fMRI study.

BACKGROUND: Studies have confirmed that the thalamus and the primary somatosensory cortex (SI) are associated with cognitive function. These two brain regions are closely related in structure and function. The interactions between SI and the thalamus are of crucial significance for the cognitive process. Patients with major depressive disorder (MDD) have significant cognitive impairment. Based on these observations, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate whether there is an abnormality in the SI-thalamic functional connection in MDD. Furthermore, we explored the clinical symptoms related to this abnormality. METHODS: We included 31 patients with first-episode major depressive disorder and 28 age-, gender-, and education-matched healthy controls (HC). The SI-thalamic functional connectivity was compared between the MDD and HC groups. The correlation analyses were performed between areas with abnormal connectivity and clinical characteristics. RESULTS: Compared with healthy subjects, the MDD patients had enhanced functional connectivity between the thalamus and SI (p < 0.05, corrected). Brain areas with significantly different levels of connectivity had a negative correlation with the Assessment of Neuropsychological Status total score (r = - 0.383, p = 0.033), delayed memory score (r = - 0.376, p = 0.037) and two-digit continuous operation test score (r = - 0.369, p = 0.041) in MDD patients. CONCLUSIONS: These results demonstrate that SI-thalamic functional connectivity is abnormal and associated with the core clinical symptoms in MDD. The SI-thalamic functional connectivity functions as a neurobiological feature and potential biomarker for MDD.

Mechanism of Cerebralcare Granule® for Improving Cognitive Function in Resting-State Brain Functional Networks of Sub-healthy Subjects.

Cerebralcare Granule® (CG), a Chinese herbal medicine, has been used to ameliorate cognitive impairment induced by ischemia or mental disorders. The ability of CG to improve health status and cognitive function has drawn researchers' attention, but the relevant brain circuits that underlie the ameliorative effects of CG remain unclear. The present study aimed to explore the underlying neurobiological mechanisms of CG in ameliorating cognitive function in sub-healthy subjects using resting-state functional magnetic resonance imaging (fMRI). Thirty sub-healthy participants were instructed to take one 2.5-g package of CG three times a day for 3 months. Clinical cognitive functions were assessed with the Chinese Revised Wechsler Adult Intelligence Scale (WAIS-RC) and Wechsler Memory Scale (WMS), and fMRI scans were performed at baseline and the end of intervention. Functional brain network data were analyzed by conventional network metrics (CNM) and frequent subgraph mining (FSM). Then 21 other sub-healthy participants were enrolled as a blank control group of cognitive functional. We found that administrating CG can improve the full scale of intelligence quotient (FIQ) and Memory Quotient (MQ) scores. At the same time, following CG treatment, in CG group, the topological properties of functional brain networks were altered in various frontal, temporal, occipital cortex regions, and several subcortical brain regions, including essential components of the executive attention network, the salience network, and the sensory-motor network. The nodes involved in the FSM results were largely consistent with the CNM findings, and the changes in nodal metrics correlated with improved cognitive function. These findings indicate that CG can improve sub-healthy subjects' cognitive function through altering brain functional networks. These results provide a foundation for future studies of the potential physiological mechanism of CG.

Cerebralcare Granule® attenuates cognitive impairment in rats continuously overexpressing microRNA-30e.

Previous studies have demonstrated that dysregulation of micro (mi)RNAs is associated with the etiology of various neuropsychiatric disorders, including depression and schizophrenia. Cerebralcare Granule® (CG) is a Chinese herbal medicine, which has been reported to have an ameliorative effect on brain injury by attenuating blood­brain barrier disruption and improving hippocampal neural function. The present study aimed to evaluate the cognitive behavior of rats continuously overexpressing miRNA­30e (lenti­miRNA­30e), prior to and following the administration of CG. In addition, the mechanisms underlying the ameliorative effects of CG were investigated. The cognitive ability of the rats was assessed using an open­field test and a Morris water maze spatial reference/working memory test. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect neuronal apoptosis in the dentate gyrus of the hippocampus. Immunohistochemical analysis and western blotting were conducted to detect the expression levels of B­cell lymphoma 2 (BCL­2) and ubiquitin­conjugating enzyme 9 (UBC9), in order to examine neuronal apoptosis. The lenti­miRNA­30e rats exhibited increased signs of anxiety, depression, hyperactivity and schizophrenia, which resulted in a severe impairment in cognitive ability. Furthermore, in the dentate gyrus of these rats, the expression levels of BCL­2 and UBC9 were reduced and apoptosis was increased. The administration of CG alleviated cognitive impairment, enhanced the expression levels of BCL­2 and UBC9, and reduced apoptosis in the dentate gyrus in the lenti­miRNA­30e rats. No significant differences were detected in behavioral indicators between the lenti­miRNA­30e rats treated with CG and the normal controls. These findings suggested that CG exerts a potent therapeutic effect, conferred by its ability to enhance the expression levels of BCL­2 and UBC9, which inhibits the apoptotic process in neuronal cells. Therefore, CG may be considered a potential therapeutic strategy for the treatment of cognitive impairment in mental disorders.

A combined study of GSK3ß polymorphisms and brain network topological metrics in major depressive disorder.

GSK3ß genotypes may interact with major depressive disorder (MDD) and may have a role in determining regional gray matter volume differences from healthy comparison subjects. However, any associations of GSK3ß genotypes with MDD related to abnormal functional brain activity have yet to be elucidated. In the present study, resting state functional brain networks were constructed by thresholding partial correlation matrices of 90 regions. Differences in the network features of GSK3ß-rs6438552 genotypes were tested, and a 2×2 analysis of variance was performed to identify the main effects of genotypes, disease status, and their interactions in MDD. Compared with CC carriers, T+ carriers with MDD showed increased nodal centralities in many brain regions-mainly the limbic system, thalamus and parts of the parietal, temporal, occipital, and frontal regions. Decreased nodal centralities predominantly occurred in the sensorimotor area and parts of the frontal, occipital, and temporal lobes. Significant interactions between genotypes and disease status were found in the left thalamus, left superior occipital gyrus, and left inferior parietal lobe. Only altered nodal centrality in the left angular gyrus was negatively correlated with scores on the Hamilton Depression Rating Scale. Our results suggest the GSK3ß genotypic effect of rs6438552 and its interaction with disease status may contribute to the altered topological organization of resting state functional brain networks in MDD patients.

Evidence of epistasis between the catechol-O-methyltransferase and aldehyde dehydrogenase 3B1 genes in paranoid schizophrenia.

BACKGROUND: Schizophrenia is a common yet severe psychiatric condition characterized by complex genetic mechanism and diverse clinical presentations. Our previous study indicated that the combined effect of two intronic single nucleotide polymorphisms (SNPs), which are located in the catechol-O-methyltransferase (COMT) and aldehyde dehydrogenase 3B1 (ALDH3B1) genes, respectively, conferred genetic risk to paranoid schizophrenia. METHODS: To further explore the precise mechanism of the COMT and ALDH3B1 interaction involved in the pathophysiology of schizophrenia, we scanned all possible functional SNPs within these two genes by polymerase chain reaction (PCR)-based genotyping analysis in 540 paranoid schizophrenic patients and 660 control subjects from a Han Chinese population. We also determined the effects of schizophrenia-associated SNPs on the development of psychotic symptoms, P300 event-related potential components induced by an auditory odd-ball task, and gene expression examined by quantitative real-time PCR analysis. RESULTS: The major findings of this study were that, among the individuals carrying the rs3751082 A allele in the ALDH3B1 gene, the rs4633 T allele in the COMT gene was associated with susceptibility to paranoid schizophrenia (p = .004), development of hallucination (p = 5.141 E-5), delay of P300 latency in both patients (p = .006) and control subjects (p = .02), and increased expression of the COMT gene in control subjects (p = .002). However, the rs4633 T allele did not show any association in the rs3751082 G/G genotype carriers. CONCLUSIONS: These findings provided convincing evidence that epistasis between the COMT and ALDH3B1 genes plays an important role in the pathogenesis of schizophrenia.